Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Abstract

The role of prostaglandins (PG), renin-angiotensin system (RAS) and calcium (Ca) in the control of renal hemodynamics and glomerular filtration rate (GFR) in chronic hypercalcemia (serum Ca 12.8 mg%) was studied. Renal blood flow (RBF, 6.39 ml/ min per gram kidney weight [gkw]) and GFR (0.52 ml/min per gkw) were significantly decreased in hy-percalcemic rats when compared with normocalcemic rats (7.15, P < 0.001 and 0.74, P < 0.05, respectively). These changes in RBF and GFR occurred independent of any significant alterations in systemic hemodynam-ics, blood and plasma volume. Inhibition of the renal PG with indomethacin resulted in marked decrements in both RBF (6.39-4.12 ml/min per gkw, P < 0.01) and GFR (0.52-0.19 ml/min per gkw, P < 0.01) in hypercalcemic rats, whereas there was no significant alterations in normocalcemic rats. Inhibition of the RAS with captopril resulted in marked increments in both RBF (6.39-7.35 ml/min per gkw, P < 0.05) and GFR (0.52-0.74 ml/min per gkw, P < 0.05) in hy-percalcemic rats. In fact, there was no significant difference from the RBF and GFR of similarly treated normocalcemic rats. Similar results were also obtained with the competitive angiotensin II (AII) antagonist (sarcosyll-isoleucyl5-glycyl8) AII. Since both the renal PG and the RAS are involved in the control of RBF and GFR in hypercalcemia, the role of each is best revealed in the absence of the other. Hence, comparison of the RBF and GFR in the PG-inhibited hyper-calcemic rats in the presence of AII (4.12 and 0.19 ml/ min per gkw, respectively) and absence of AII (5.99 and 0.53 ml/min per gkw, P < 0.01 for both) reveals the vasoconstrictive role for All in hypercalcemia. On the other hand, comparison of the RBF and GFR in the AII-inhibited hypercalcemic rats in the presence of PG (7.35 and 0.74 ml/min per gkw, respectively) and absence of PG (5.99 and 0.53 ml/min per gkw, P < 0.01 and P < 0.05, respectively) reveals the va-sodilatory role for PG in hypercalcemia. Finally, comparison of the RBF and GFR in both PG-and All-inhibited hypercalcemic rats (5.99 and 0.53 ml/min per gkw, respectively) with similarly treated normo-calcemic rats (7.30 and 0.94 ml/min per gkw, P < 0.001 and P < 0.005, respectively) reveals the va-soconstrictive role for Ca in chronic hypercalcemia. Our study therefore demonstrates that in chronic hy-percalcemia the RBF and GFR are controlled by an active interplay of the vasoconstrictive effect of AII, the vasodilatory effect of renal PG, and the direct va-soconstrictive effect of Ca, independent of either AII or PG. The sum total of these forces produces a modest but significant decrease in RBF and GFR. INTRODUCTION The association of acute and chronic hypercalcemia with decrements in renal blood flow (RBF)' and glo-merular filtration rate (GFR) has been widely recognized in both man and experimental animals (1-15). While the mechanisms responsible for the decrement in RBF and GFR have been studied in anesthetized, acutely hypercalcemic animals, there have been no such studies in the setting of chronic hypercalcemia. Since recent in vivo and in vitro studies have revealed ' Abbreviations used in this paper: AII, angiotensin